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MGP002112

UniProt Annotations

Entry Information
Gene Namenitric oxide synthase 3 (endothelial cell)
Protein EntryNOS3_HUMAN
UniProt IDP29474
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P29474-1; Sequence=Displayed; Name=eNOS13C; IsoId=P29474-2; Sequence=VSP_042625, VSP_042626; Note=Lacks eNOS activity.; Name=eNOS13B; IsoId=P29474-3; Sequence=VSP_045495, VSP_045496;
Catalytic Activity2 L-arginine + 3 NADPH + 4 O(2) = 2 L- citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O.
CofactorName=5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:15372; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;
CofactorName=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.;
CofactorName=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.;
CofactorName=heme; Xref=ChEBI:CHEBI:30413;
Enzyme RegulationStimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN. {ECO:0000269|PubMed:11149895, ECO:0000269|PubMed:12446846}.
FunctionIsoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
FunctionProduces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
InteractionP31749:AKT1; NbExp=2; IntAct=EBI-1391623, EBI-296087; Q16543:CDC37; NbExp=4; IntAct=EBI-1391623, EBI-295634; Q8IVI9:NOSTRIN; NbExp=9; IntAct=EBI-1391623, EBI-1391643; P50502:ST13; NbExp=3; IntAct=EBI-1391623, EBI-357285; P14079:tax (xeno); NbExp=3; IntAct=EBI-1391623, EBI-9675698;
PolymorphismVariation in NOS3 seem to be associated with susceptibility to coronary spasm.
PtmPhosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of Ca(2+)- calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity). Phosphorylation of Ser-114 by CDK5 reduces activity. {ECO:0000250, ECO:0000269|PubMed:16126727, ECO:0000269|PubMed:20213743}.
SimilarityBelongs to the NOS family. {ECO:0000305}.
SimilarityContains 1 FAD-binding FR-type domain. {ECO:0000255|PROSITE-ProRule:PRU00716}.
SimilarityContains 1 flavodoxin-like domain. {ECO:0000255|PROSITE-ProRule:PRU00088}.
Subcellular LocationCell membrane. Membrane, caveola. Cytoplasm, cytoskeleton. Golgi apparatus. Note=Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle; which is favored by interaction with NOSIP and results in a reduced enzymatic activity.
SubunitHomodimer. Interacts with NOSIP and NOSTRIN. {ECO:0000269|PubMed:11149895, ECO:0000269|PubMed:12446846}.
Tissue SpecificityPlatelets, placenta, liver and kidney. {ECO:0000269|PubMed:7515611}.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/nos3/";
Web ResourceName=Wikipedia; Note=Nitric oxide synthase entry; URL="http://en.wikipedia.org/wiki/Nitric_oxide_synthase";
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